Mitochondrial dysfunction is at the core of many encephalomyopathies, diabetes and cancer. Inherited mutations in over 100 genes constituting the oxidative phosphorylation (OxPhos) machinery are linked with mitochondrial encephalomyopathies in humans. The diseases resulting from defective OxPhos are also referred to as mitochondrial diseases or mitochondrial disorders. They are usually multisystemic fatal disorders with progressive onset with age Impaired mitochondrial metabolism is also thought to play a key role in the pathophysiology of diabetes and cancer. Mutational analysis of mitochondrial (mt)DNA suggests that mitochondrial dysfunction is a widespread phenomenon, which occurs in almost all types of cancers. Somatic mutations in the mtDNA, which encodes proteins essential for OxPhos, are found associated with almost all types of cancer. However, their functional relevance is yet to be determined in most cases.
The COSMIC (Catalogue Of Somatic Mutations In Cancer) database reveals that mutations in nuclear genes associated with oxidative phosphorylation functions is common. Somatic mutations in over 25 nuclear genes associated with respiratory Complex I (NADH-ubiquinone oxidoreductase) structure/function have been identified. In addition, switching of the cellular metabolism from oxidative metabolism to glycolysis, which is known as metabolic reprogramming, is one of the hallmarks of cancer phenotypes. This could be due to somatic mutations in mtDNA, nDNA or negative regulation of the oxidative phosphorylation due to host and environmental factors. Mitochondrial dysfunction is also implicated in other age-associated diseases such as Parkinson's disease, and Alzheimer's disease. Thus, there is an need for simple and accurate methods to assess the mitochondrial function in the context of pathophysiology. Such methods can lead to determinations of “cause and effect” relationships between the mitochondrial metabolism and pathophysiology, and efficacies of therapeutic interventions in restoring normal mitochondrial metabolism. Accordingly, methods for accurately measuring mitochondrial function are important not only for detecting and understanding these diseases, but also for evaluating therapies and other treatments that impact oxidative phosphorylation
In terms of cellular bioenergetics, it can be useful to determine the reserve (spare) capacity of mitochondria to make ATP (the oxidative phosphorylation capacity), and its relationship with the maximal oxygen consumption by the respiratory chain (the respiratory capacity), which determine the fate of cells under conditions of acute/high ATP demand.